EP0356024B1 - Use of dextrin derivatives for the treatment of acidic conditions - Google Patents
Use of dextrin derivatives for the treatment of acidic conditions Download PDFInfo
- Publication number
- EP0356024B1 EP0356024B1 EP89307738A EP89307738A EP0356024B1 EP 0356024 B1 EP0356024 B1 EP 0356024B1 EP 89307738 A EP89307738 A EP 89307738A EP 89307738 A EP89307738 A EP 89307738A EP 0356024 B1 EP0356024 B1 EP 0356024B1
- Authority
- EP
- European Patent Office
- Prior art keywords
- dextrin
- pharmaceutical composition
- composition according
- groups
- derivative
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 229920001353 Dextrin Polymers 0.000 title claims abstract description 57
- 239000004375 Dextrin Substances 0.000 title claims abstract description 57
- 235000019425 dextrin Nutrition 0.000 title claims abstract description 57
- 230000002378 acidificating effect Effects 0.000 title abstract description 7
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims abstract description 17
- 210000004369 blood Anatomy 0.000 claims abstract description 8
- 239000008280 blood Substances 0.000 claims abstract description 8
- 231100000572 poisoning Toxicity 0.000 claims abstract description 7
- 230000000607 poisoning effect Effects 0.000 claims abstract description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 14
- 239000008103 glucose Substances 0.000 claims description 13
- 229920000642 polymer Polymers 0.000 claims description 13
- 125000003277 amino group Chemical group 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 239000002671 adjuvant Substances 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000001453 quaternary ammonium group Chemical group 0.000 claims description 4
- 210000004303 peritoneum Anatomy 0.000 claims description 3
- 150000003512 tertiary amines Chemical class 0.000 claims description 3
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 claims 2
- 239000003613 bile acid Substances 0.000 abstract description 7
- 231100000614 poison Toxicity 0.000 abstract description 6
- 239000002574 poison Substances 0.000 abstract description 4
- 241001465754 Metazoa Species 0.000 abstract description 2
- 208000003870 Drug Overdose Diseases 0.000 abstract 1
- 241000282414 Homo sapiens Species 0.000 abstract 1
- 206010033296 Overdoses Diseases 0.000 abstract 1
- 231100000725 drug overdose Toxicity 0.000 abstract 1
- 239000000203 mixture Substances 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 239000000243 solution Substances 0.000 description 9
- 238000000502 dialysis Methods 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 229920001268 Cholestyramine Polymers 0.000 description 6
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 6
- 229960002695 phenobarbital Drugs 0.000 description 6
- 208000005374 Poisoning Diseases 0.000 description 5
- 229920002472 Starch Polymers 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 239000003792 electrolyte Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 210000003200 peritoneal cavity Anatomy 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- WBWWGRHZICKQGZ-HZAMXZRMSA-N taurocholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCS(O)(=O)=O)C)[C@@]2(C)[C@@H](O)C1 WBWWGRHZICKQGZ-HZAMXZRMSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- WBWWGRHZICKQGZ-UHFFFAOYSA-N Taurocholic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(=O)NCCS(O)(=O)=O)C)C1(C)C(O)C2 WBWWGRHZICKQGZ-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 210000000936 intestine Anatomy 0.000 description 3
- 239000002357 osmotic agent Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 229960001138 acetylsalicylic acid Drugs 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- VIROVYVQCGLCII-UHFFFAOYSA-N amobarbital Chemical compound CC(C)CCC1(CC)C(=O)NC(=O)NC1=O VIROVYVQCGLCII-UHFFFAOYSA-N 0.000 description 2
- 239000003957 anion exchange resin Substances 0.000 description 2
- 210000003567 ascitic fluid Anatomy 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000005194 fractionation Methods 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 210000002381 plasma Anatomy 0.000 description 2
- 229920002959 polymer blend Polymers 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 1
- 206010000489 Acidosis hyperchloraemic Diseases 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 240000008886 Ceratonia siliqua Species 0.000 description 1
- 235000013912 Ceratonia siliqua Nutrition 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 229920002911 Colestipol Polymers 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 244000303965 Cyamopsis psoralioides Species 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 206010014418 Electrolyte imbalance Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 240000004584 Tamarindus indica Species 0.000 description 1
- 235000004298 Tamarindus indica Nutrition 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 206010000059 abdominal discomfort Diseases 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 229960001301 amobarbital Drugs 0.000 description 1
- 238000005349 anion exchange Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229940125717 barbiturate Drugs 0.000 description 1
- 229960003874 butobarbital Drugs 0.000 description 1
- STDBAQMTJLUMFW-UHFFFAOYSA-N butobarbital Chemical compound CCCCC1(CC)C(=O)NC(=O)NC1=O STDBAQMTJLUMFW-UHFFFAOYSA-N 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 150000003841 chloride salts Chemical class 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229960002577 colestipol hydrochloride Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- -1 diethyl pentamine Chemical compound 0.000 description 1
- 102000038379 digestive enzymes Human genes 0.000 description 1
- 108091007734 digestive enzymes Proteins 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 201000006549 dyspepsia Diseases 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- GACQNVJDWUAPFY-UHFFFAOYSA-N n'-[2-[2-(2-aminoethylamino)ethylamino]ethyl]ethane-1,2-diamine;hydrochloride Chemical compound Cl.NCCNCCNCCNCCN GACQNVJDWUAPFY-UHFFFAOYSA-N 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000007096 poisonous effect Effects 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229960002060 secobarbital Drugs 0.000 description 1
- KQPKPCNLIDLUMF-UHFFFAOYSA-N secobarbital Chemical compound CCCC(C)C1(CC=C)C(=O)NC(=O)NC1=O KQPKPCNLIDLUMF-UHFFFAOYSA-N 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B31/00—Preparation of derivatives of starch
- C08B31/08—Ethers
- C08B31/12—Ethers having alkyl or cycloalkyl radicals substituted by heteroatoms, e.g. hydroxyalkyl or carboxyalkyl starch
- C08B31/125—Ethers having alkyl or cycloalkyl radicals substituted by heteroatoms, e.g. hydroxyalkyl or carboxyalkyl starch having a substituent containing at least one nitrogen atom, e.g. cationic starch
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
Definitions
- This invention relates to the treatment of acidic conditions and to compositions for use in such treatment.
- Cholestyramine is the chloride salt of a basic anion-exchange resin in which the anion-exchange sites are provided by quaternary ammonium groups.
- the other agent is a resin called colestipol hydrochloride, a copolymer of diethyl pentamine and epichlorohydrin. Both these materials are hydrophilic but insoluble in water.
- Another problem with these known agents is that they may also bind other compounds in the intestine including drugs administered concurrently.
- Acid poisoning can occur as a result not only of the assimilation of substances which are normally regarded as poisons but also of pharmaceutical preparations which can be poisonous if taken in overdose.
- acid poisons include acetylsalicylic acid (aspirin) and barbiturates such as amylobarbitone, butobarbitone, pentobarbitone, phenobarbitone and quinalbarbitone.
- EP-A-0212145 discloses the use of certain quaternary ammonium salts of natural polysaccharides, specifically tragacanth, guar and carob gums, cellulose, tamarind and chitosan, in the treatment of hypercholesterolaemia.
- a pharmaceutical composition comprising a dextrin derivative in which a proportion of the hydroxyl groups of dextrin are replaced by amine groups and a pharmaceutically acceptable diluent, carrier and/or adjuvant.
- a preferred amine group is a tertiary amine or a quaternary ammonium group.
- the present invention accordingly also provides the use of a dextrin derivative in which a proportion of the hydroxyl groups of dextrin are replaced by amine groups in the manufacture of a pharmaceutical composition for treating acid poisoning and/or lowering blood cholesterol levels.
- the invention provides a method of making a pharmaceutical composition
- a method of making a pharmaceutical composition comprising formulating together a dextrin derivative in which a proportion of the hydroxyl groups of dextrin are replaced by amine groups and an inert carrier, diluent and/or adjuvant.
- Dextrin is made by hydrolysis of starch, typically by treatment of various starches with dilure acids or by heating a dry starch. Such methods produce glucose polymers with a wide range of polymerisation.
- the degree of polymerisation (D.P.) varies from one or two up to comparatively high numbers.
- the direct hydrolysis product of starch might contain up to 60% by weight of material having a D.P. less than 12.
- the dextrin derivative contains a relatively high proportion of glucose polymers of D.P. greater than 12.
- the dextrin derivative contains at least 50% by weight of glucose polymers of D.P. greater than 12.
- the dextrin derivative contains less than 10% by weight of glucose polymers having a D.P. less than 12. Most preferably the dextrin derivative contains less than 5% by weight of glucose polymers having a D.P. less than 12.
- Such dextrin derivatives are prepared from dextrin which has been fractionated to remove dextrin with a low D.P. Known fractionation techniques may be used including solvent precipation and membrane fractionation.
- a method of preparing a glucose polymer mixture is described in GB 2132914 and a method for the preparation of a glucose polymer mixture with a relatively low proportion of low D.P. glucose polymers is described in Example 2 of GB 2154469.
- This mixture contains 91.9% of polymers having a degree of polymerisation greater than 12 and 7.9% of polymers having a degree of polymerisation from 2 to 10.
- the weight average molecular weight of the dextrin derivative of use in the present invention is preferably from 15,000 to 25,000, more preferably from 15,000 to 20,000.
- the number average molecular weight is preferably less than 5,000.
- the weight average molecular weight is determined by high pressure liquid chromatography (HPLC). The method is carried out on dextrin (rather than the dextrin derivative) using chromatographic columns calibrated with dextran standards, as descrived by Alsop et al, J. Chromatography 246, 227-240 (1982).
- the very high molecular weight glucose polymers are not present or are only present in small amounts in the dextrin derivative mixture.
- composition in accordance with the present invention may be made up for administration by any suitable route.
- the composition may be for oral administration or, in the case of treatment of acid poisoning, for administration via the peritoneum.
- the derivatives of use in the pharmaceutical composition of the invention can be prepared in various ways. For instance, they may be prepared by methods analogous to those described for the preparation of ethers having a tertiary amine group as described in US 2813093, US 2917506, US 2935436 and US 2975124, or, for the preparation of quaternary ammonium compounds, as described in US 2876217.
- the properties of basic derivatives of dextrin depend on the nature and content of the basic groups. It is preferred that the derivative is water soluble.
- the content of the basic group is preferably at least 5% by weight, the upper limit being determined in practice by the difficulty of introducing much more than 10% by weight of the basic group into the dextrin, using currently available techniques.
- compositions containing derivatives of dextrin can be used. These compositions have the advantage that they are water soluble and their taste or colour can be disguised by adding, for instance, synthetic food additives.
- the active material By drinking a mixture containing the dextrin derivative the active material immediately reaches the intestine where it acts to bind bile acids or acid poisions.
- the rapid delivery of the active ingredient to its target, the bile acids or the acid poisons has the advantage that no degeneration occurs before the active ingredient reaches the site of the target.
- a composition for peritoneal administration may also include electrolytes similar to those contained in conventional solutions used in peritoneal dialysis. For example, they may include electrolytes in the following concentration (all in mmol/l):- Na 115 to 140 Cl 95 to 145 Mg 0.6 to 0.9 Ca 1.0 to 5.0 Lactate 30 to 40.
- electrolytes are, however, not so important as in conventional peritoneal dialysis, because the treatment of cholesterol levels or of acid poisoning is a short-term operation. Nevertheless, electrolyte imbalance can cause serious problems in poisoned patients, and the present of suitable electrolytes in the dialysis is recommended.
- compositions of the invention contain an osmotic agent in a concentration capable of producing efficient and sustained ultrafiltration (a term used to mean the net flow of fluid across the peritoneal membrane into the peritoneal cavity).
- the osmotic agent in the compositions of the invention is normally the dextrin derivative itself, although it can be supplemented, when appropriate, by the inclusion of other osmotic agents, for example dextrose or a mixture of glucose polymers.
- a quaternary ammonium alkyl dextrin (specifically quaternary ammonium hydroxyethyl dextrin) was prepared in the following manner. Triethylamine (45 g) was suspended in water (100 ml) and stirred at room temperature. Then epichlorohydrin (37g, 0.4 mole) was added dropwise. Stirring was continued for 5 hours but the mixture was still not homogeneous. After stirring overnight the resultant homogeneous solution was evaporated at 30°C in vacuo to a thick syrup over several hours.
- the substituted dextrin can accordingly be used to lower blood cholesterol levels but without the above mentioned disadvantages associated with the use of cholestyramine.
- Rats were dosed intravenously with radio-labelled phenobarbitone and after 15 minutes 10 ml of a 2% solution of the dextrin derivative was introduced into the peritoneum. For comparison a 2% solution of unsubstituted dextrin was used as a control. The experiment was conducted on two occasions with 3 animals in each treatment group. One hour after the introduction of the solutions into the peritoneal cavity, simultaneous samples of blood and peritoneal fluid were obtained and analysed for radio-labelled phenobarbitone. Peritoneal fluid/blood plasma ratios for phenobarbitone at 3 hours are given below. Dialysate Dialysate fluid/blood plasma ratio Experiment 1 Experiment 2 2% Dextrin 0.89 0.94 2% Dextrin derivative 2.32 2.68
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Materials Engineering (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Polymers & Plastics (AREA)
- Biochemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Steroid Compounds (AREA)
- Saccharide Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Eye Examination Apparatus (AREA)
- Separation Using Semi-Permeable Membranes (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB888818116A GB8818116D0 (en) | 1988-07-29 | 1988-07-29 | Compounds & compositions for medical treatment |
GB8818116 | 1988-07-29 |
Publications (2)
Publication Number | Publication Date |
---|---|
EP0356024A1 EP0356024A1 (en) | 1990-02-28 |
EP0356024B1 true EP0356024B1 (en) | 1995-05-03 |
Family
ID=10641334
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP89307738A Expired - Lifetime EP0356024B1 (en) | 1988-07-29 | 1989-07-28 | Use of dextrin derivatives for the treatment of acidic conditions |
EP89909226A Pending EP0427779A1 (en) | 1988-07-29 | 1989-07-28 | Use of dextrin derivatives for the treatment of acidic conditions |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP89909226A Pending EP0427779A1 (en) | 1988-07-29 | 1989-07-28 | Use of dextrin derivatives for the treatment of acidic conditions |
Country Status (18)
Country | Link |
---|---|
US (2) | US5280017A (pt) |
EP (2) | EP0356024B1 (pt) |
JP (1) | JPH04500976A (pt) |
AT (1) | ATE122058T1 (pt) |
AU (1) | AU626074B2 (pt) |
CA (1) | CA1337517C (pt) |
DE (1) | DE68922445T2 (pt) |
DK (1) | DK308990A (pt) |
ES (1) | ES2072904T3 (pt) |
FI (1) | FI100534B (pt) |
GB (1) | GB8818116D0 (pt) |
HR (1) | HRP920595A2 (pt) |
NO (1) | NO910316D0 (pt) |
NZ (1) | NZ230147A (pt) |
PT (1) | PT91332B (pt) |
WO (1) | WO1990001499A1 (pt) |
YU (1) | YU47421B (pt) |
ZA (1) | ZA895705B (pt) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB8818116D0 (en) * | 1988-07-29 | 1988-09-01 | D S Pharmaceuticals Ltd | Compounds & compositions for medical treatment |
GB9001687D0 (en) * | 1990-01-25 | 1990-03-28 | Ml Lab Plc | Treatment of poisoning and composition for use therein |
SE503134C2 (sv) * | 1994-02-16 | 1996-04-01 | Sveriges Staerkelseproducenter | Stärkelse av dextrintyp, sätt att framställa denna samt dess användning som energipreparat |
GB9810127D0 (en) * | 1998-05-13 | 1998-07-08 | Ml Lab Plc | Prevention of surgical adhesions |
Family Cites Families (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NL275026A (pt) * | 1953-06-10 | |||
US3639389A (en) * | 1968-05-15 | 1972-02-01 | Cpc International Inc | Low d.e. starch hydrolysate derivatives |
GB1576325A (en) * | 1976-06-04 | 1980-10-08 | Procter & Gamble | Textile treatment compositions |
DE2724816A1 (de) * | 1976-06-04 | 1977-12-15 | Procter & Gamble Europ | Textil-behandlungsmittel |
US4179382A (en) * | 1977-11-21 | 1979-12-18 | The Procter & Gamble Company | Textile conditioning compositions containing polymeric cationic materials |
US4129722A (en) * | 1977-12-15 | 1978-12-12 | National Starch And Chemical Corporation | Process for the preparation of high D. S. polysaccharides |
JPS6042766B2 (ja) * | 1978-12-09 | 1985-09-25 | 日本化薬株式会社 | 基剤 |
IT1144697B (it) * | 1981-04-06 | 1986-10-29 | Texcontor Ets | Derivato semi-sintetico della chitina processo per la sua preparazione e composizioni terapeutiche che lo comprendono come principio attivo |
SE8103137L (sv) * | 1981-05-19 | 1982-11-20 | Pharmacia Ab | Polymer med kvartera aminogrupper |
GB8404299D0 (en) * | 1984-02-18 | 1984-03-21 | Milner Research Ireland Ltd | Peritoneal dialysis |
IT1188184B (it) * | 1985-08-14 | 1988-01-07 | Texcontor Ets | Sali ammonici quaternari di polisaccaridi ad attivita' ipocolesterolemizzante |
IT1223362B (it) * | 1987-11-20 | 1990-09-19 | Texcontor Ets | Derivati cationizzati polisaccaridi ad attivita' ipocolesterolemizzante |
GB8818116D0 (en) * | 1988-07-29 | 1988-09-01 | D S Pharmaceuticals Ltd | Compounds & compositions for medical treatment |
GB9001687D0 (en) * | 1990-01-25 | 1990-03-28 | Ml Lab Plc | Treatment of poisoning and composition for use therein |
US5169562A (en) * | 1990-03-27 | 1992-12-08 | W. R. Grace & Co.-Conn. | Emulsion breaking using cationic quaternary ammonium starch/gums |
-
1988
- 1988-07-29 GB GB888818116A patent/GB8818116D0/en active Pending
-
1989
- 1989-07-27 YU YU150589A patent/YU47421B/sh unknown
- 1989-07-27 ZA ZA895705A patent/ZA895705B/xx unknown
- 1989-07-28 AT AT89307738T patent/ATE122058T1/de not_active IP Right Cessation
- 1989-07-28 AU AU40508/89A patent/AU626074B2/en not_active Ceased
- 1989-07-28 JP JP1508598A patent/JPH04500976A/ja active Pending
- 1989-07-28 US US07/640,313 patent/US5280017A/en not_active Expired - Fee Related
- 1989-07-28 DE DE68922445T patent/DE68922445T2/de not_active Expired - Fee Related
- 1989-07-28 ES ES89307738T patent/ES2072904T3/es not_active Expired - Lifetime
- 1989-07-28 EP EP89307738A patent/EP0356024B1/en not_active Expired - Lifetime
- 1989-07-28 WO PCT/GB1989/000858 patent/WO1990001499A1/en active IP Right Grant
- 1989-07-28 EP EP89909226A patent/EP0427779A1/en active Pending
- 1989-07-31 PT PT91332A patent/PT91332B/pt not_active IP Right Cessation
- 1989-07-31 NZ NZ230147A patent/NZ230147A/xx unknown
- 1989-07-31 CA CA000607119A patent/CA1337517C/en not_active Expired - Fee Related
-
1990
- 1990-12-28 DK DK308990A patent/DK308990A/da not_active Application Discontinuation
-
1991
- 1991-01-21 FI FI910296A patent/FI100534B/fi active
- 1991-01-28 NO NO910316A patent/NO910316D0/no unknown
-
1992
- 1992-09-29 HR HRP920595 patent/HRP920595A2/hr not_active Application Discontinuation
-
1993
- 1993-11-12 US US08/150,717 patent/US5439894A/en not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
YU150589A (en) | 1991-02-28 |
NO910316L (no) | 1991-01-28 |
DK308990A (da) | 1991-01-28 |
DE68922445D1 (de) | 1995-06-08 |
CA1337517C (en) | 1995-11-07 |
NO910316D0 (no) | 1991-01-28 |
AU626074B2 (en) | 1992-07-23 |
ZA895705B (en) | 1990-04-25 |
EP0427779A1 (en) | 1991-05-22 |
US5439894A (en) | 1995-08-08 |
NZ230147A (en) | 1991-11-26 |
ES2072904T3 (es) | 1995-08-01 |
GB8818116D0 (en) | 1988-09-01 |
WO1990001499A1 (en) | 1990-02-22 |
FI910296A0 (fi) | 1991-01-21 |
JPH04500976A (ja) | 1992-02-20 |
PT91332A (pt) | 1990-02-08 |
FI100534B (fi) | 1997-12-31 |
PT91332B (pt) | 1995-03-01 |
DE68922445T2 (de) | 1995-11-02 |
DK308990D0 (da) | 1990-12-28 |
EP0356024A1 (en) | 1990-02-28 |
US5280017A (en) | 1994-01-18 |
YU47421B (sh) | 1995-03-27 |
AU4050889A (en) | 1990-03-05 |
ATE122058T1 (de) | 1995-05-15 |
HRP920595A2 (pt) | 1995-10-31 |
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